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Intronic alternative splicing regulators identified by comparative genomics in nematodes
Jennifer L Kabat1, Sergio Barberan-Soler, Paul McKenna
1Department of Molecular, Cell, and Developmental Biology and Center for Molecular Biology of RNA, University of California Santa Cruz, Santa Cruz, California, USA.
Plos Computational Biology
|July 15, 2006
Summary
Conserved intronic elements regulate alternative splicing. Focusing on these conserved regions enhances the detection of splicing motifs and reveals novel regulatory sequences, advancing our understanding of splicing regulation across species.
Area of Science:
- Genomics
- Molecular Biology
- Evolutionary Biology
Background:
- Alternative splicing is crucial for gene expression, often regulated by intronic sequences binding splicing factors.
- Evolutionary conservation of these regulatory elements suggests functional importance.
Purpose of the Study:
- To investigate if intronic elements regulating alternative splicing are evolutionarily conserved.
- To identify conserved intronic motifs associated with alternative splicing regulation.
- To develop a catalog of splicing regulatory elements.
Main Methods:
- Genomic alignment of *Caenorhabditis elegans* and *Caenorhabditis briggsae* to identify conserved intronic regions flanking alternatively spliced exons.
- Analysis of pentamer and hexamer motif frequencies in conserved intronic elements compared to all intron sequences.
- In vivo experiments to validate the regulatory role of identified conserved sequences.
Main Results:
- Identified 147 alternatively spliced cassette exons with conserved intronic regions.
- Discovered numerous high-scoring pentamer and hexamer motifs in conserved elements, many matching known mammalian splicing regulators.
- Validated a novel motif, (T)CTATC, as important for alternative splicing regulation of the *unc-52* gene.
- Demonstrated that focusing on intronic conservation improves the detection sensitivity of splicing regulatory motifs.
Conclusions:
- Intronic elements regulating alternative splicing are under selective pressure for evolutionary conservation.
- Conserved intronic sequences provide a sensitive approach to identify splicing regulatory motifs, including novel ones.
- The findings suggest conserved mechanisms of alternative splicing regulation across metazoans.